Advancements in therapies for patients with cystic fibrosis (CF) have decreased mortality, leading to increased prevalence of chronic complications including bone disease. CF-related bone disease (CFBD) is characterized by low bone mineral density (BMD) and fragility fractures. Estrogen deficiency increases bone resorption, resulting in decreased BMD that can be restored with estrogen replacement. Current CF guidelines recommend treating female hypogonadal patients with CFBD with estrogen replacement, but no prospective study has investigated the effects of estrogen supplementation on CFBD. Estrogen is known to modulate inflammatory markers and autoimmune diseases. We proposed to test the hypothesis that estrogen status plays a critical role in optimizing bone health, modulating inflammation, preserving lung function, and maximizing quality of life in premenopausal women with CF. We planned a randomized, placebo-controlled, investigator- and patient-blinded, pilot trial with two parallel arms. Eligible subjects were women with CF 18–50 years old with hypogonadism and low BMD who were not taking systemic glucocorticoids, had not had a prior transplant, and did not have contraindications to oral estradiol. Subjects would be block randomized to receive oral estradiol or placebo for 6 months. The primary outcome was feasibility metrics. Secondary outcomes included relative changes in estradiol, bone turnover markers, lung function, inflammatory markers, and quality of life metrics. The study was funded through departmental funds. Of 233 subjects screened, 86 subjects were women with CF 18–50 years old and none were eligible for participation. Most subjects were excluded due to absent DXA report (24%), normal BMD (22%), or use of systemic estrogen (16%). Due to difficulty recruiting the planned 52 subjects, the trial was closed for recruitment and no subjects were randomized. This study was designed to investigate the feasibility of a safety and efficacy trial of estrogen therapy for women with CF. Unfortunately, due to eligibility criteria, the study was unable to recruit subjects. This feasibility study highlights the need for improved BMD screening in young women with CF. Future study designs may require the incorporation of a screening DXA as part of subject recruitment. The study was registered on ClinicalTrials.gov ( NCT03724955 ).

中文翻译：

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雌二醇用于患有囊性纤维化相关骨病的性腺功能减退女性的可行性研究结果

囊性纤维化 (CF) 患者治疗的进步降低了死亡率，导致包括骨病在内的慢性并发症的患病率增加。CF 相关骨病 (CFBD) 的特征是低骨密度 (BMD) 和脆性骨折。雌激素缺乏会增加骨吸收，导致骨密度降低，而这可以通过雌激素替代来恢复。目前的 CF 指南建议用雌激素替代治疗患有 CFBD 的女性性腺功能减退患者，但没有前瞻性研究调查补充雌激素对 CFBD 的影响。已知雌激素可调节炎症标志物和自身免疫性疾病。我们提议检验雌激素状态在优化骨骼健康、调节炎症、保护肺功能、并最大限度地提高绝经前 CF 妇女的生活质量。我们计划了一项随机、安慰剂对照、研究者和患者盲法的试验性试验，其中有两个平行组。符合条件的受试者是 18-50 岁患有性腺机能减退和 BMD 低的 CF 女性，她们没有服用全身性糖皮质激素，之前没有接受过移植手术，并且没有口服雌二醇的禁忌症。受试者将被随机分组​​接受口服雌二醇或安慰剂 6 个月。主要结果是可行性指标。次要结果包括雌二醇、骨转换标志物、肺功能、炎症标志物和生活质量指标的相对变化。该研究由部门资金资助。在筛选的 233 名受试者中，86 名受试者是 18-50 岁的 CF 女性，没有人符合参与条件。由于缺乏 DXA 报告 (24%)、正常 BMD (22%) 或使用全身雌激素 (16%)，大多数受试者被排除在外。由于难以招募计划的 52 名受试者，该试验已结束招募，没有受试者被随机分配。本研究旨在调查雌激素疗法对 CF 女性的安全性和有效性试验的可行性。不幸的是，由于资格标准，该研究无法招募受试者。这项可行性研究强调了改善年轻 CF 女性 BMD 筛查的必要性。未来的研究设计可能需要纳入筛选 DXA 作为受试者招募的一部分。该研究已在 ClinicalTrials.gov (NCT03724955) 上注册。该试验已结束招募，没有受试者被随机分配。本研究旨在调查雌激素疗法对 CF 女性的安全性和有效性试验的可行性。不幸的是，由于资格标准，该研究无法招募受试者。这项可行性研究强调了改善年轻 CF 女性 BMD 筛查的必要性。未来的研究设计可能需要纳入筛选 DXA 作为受试者招募的一部分。该研究已在 ClinicalTrials.gov (NCT03724955) 上注册。该试验已结束招募，没有受试者被随机分配。本研究旨在调查雌激素疗法对 CF 女性的安全性和有效性试验的可行性。不幸的是，由于资格标准，该研究无法招募受试者。这项可行性研究强调了改善年轻 CF 女性 BMD 筛查的必要性。未来的研究设计可能需要纳入筛选 DXA 作为受试者招募的一部分。该研究已在 ClinicalTrials.gov (NCT03724955) 上注册。这项可行性研究强调了改善年轻 CF 女性 BMD 筛查的必要性。未来的研究设计可能需要纳入筛选 DXA 作为受试者招募的一部分。该研究已在 ClinicalTrials.gov (NCT03724955) 上注册。这项可行性研究强调了改善年轻 CF 女性 BMD 筛查的必要性。未来的研究设计可能需要纳入筛选 DXA 作为受试者招募的一部分。该研究已在 ClinicalTrials.gov (NCT03724955) 上注册。